tbuckley/cabot-search huggingface dataset:
AB1703 EVALUATION OF A TRAINING COURSE ON BREAKING BAD NEWS IN RHEUMATOLOGY
Authors: G. Khaldi, S. Miladi, W. Abdelghaffar, A. Fazaa, H. Boussaa, M. Yasmine, K. Ben Abdelghani, R. Rafrafi, M. A. Laatar
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Although communication skills towards breaking bad news are an important aspect of medical care [1], future Tunisian rheumatologists have no formal training in this area. The gaps in communication skills are significant to date in the field of rheumatology. <h3>Objectives</h3> The aim of this study was to evaluate the impact of a training workshop on the disclosure of bad news in rheumatology. <h3>Methods</h3> We conducted a prospective, multicenter, interventional study over a six-month period during the academic year 2021-2022. 31 residents were recruited on a voluntary basis. Two groups were individualized: The training group A (N=16) and the control group B (N=15). The training session included interactive lectures, video-case studies, role-playing and peer-to-peer discussions. A self-administered survey was used to assess residents' abilities to deliver bad news before and three months after the training. <h3>Results</h3> Following training (T3), group A residents showed a significant improvement in their ability to plan the announcement consultation (p=0.004), prepare the patient for the announcement of bad news (p=0.009), deliver the bad news itself (p=0.003), as well as in their self-assigned skill level (p=0.003). Their post-training ratings were significantly better than those of control group B. However, the training group's progress in handling patients' emotions was not statistically significant (p=0.488), and there was no distinction between the two groups after the training. Although both groups of residents were quite adept at managing their stress, their reactions to the announcement were primarily negative (sorrow and sadness). The inclusion of this training in the rheumatology curriculum received "extremely important" or "important" ratings from all residents (100%). when looking at the determinants of a successful announcement, the year of residency was the only factor that showed a statistically significant association with enhanced theoretical knowledge (p = 0.049). <h3>Conclusion</h3> This study highlighted the improvement of the residents' competencies as well as their self-assigned skill level related to the use of role-play in the acquisition of competencies related to a particular situation such as the announcement of bad news. The training seminar on breaking bad news was beneficial and had a positive impact on the residents' performance. It enabled them to pick up several new abilities. <h3>Reference</h3> [<b>1]</b> Kurer MA, Zekri JM. Breaking bad news: can we get it right? Libyan J Med. 2008 Dec;3(4):200-3. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
AB1715 ASSESSING KNOWLEDGE AND PRACTICES OF MOROCCAN RHEUMATOLOGISTS ON PNEUMOCOCCAL VACCINATION IN PATIENTS WITH CHRONIC INFLAMMATORY RHEUMATIC DISEASES(CIRD)
Authors: S. Ez-Zaoui, H. Rkain, F. Kronbi, T. Latifa, S. Bahloul, I. Bensaghir, R. Honsali, S. Farih, F. El Joumani, N. Hajjaj-Hassouni, F. Allali
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background:</h3> <h3>Objectives</h3> To assess rheumatologists' knowledge and practice about pneumococcal vaccination in patients with CIRD. <h3>Methods</h3> This is a cross-sectional study conducted by the vaccination working group of the Moroccan Society of Rheumatology. The survey collected data on the knowledge and practice of pneumococcal vaccination by rheumatologists. <h3>Results</h3> Out of 350 questionnaires sent, 125 valid responses were received (35%).The mean age of rheumatologists was 42.4+/-12.1 years and the average duration of practicing in rheumatology was 13.1+/-11.1 years. The sector of practice was respectively 31.2 %,34.4 %,34.4 % for the public, private and Univesity Hospital sectors. Knowledge accurency about the nature of vaccine and vaccination protocol was noted in respectively 62.4% and 46.4% of rheumatologists. Figure 1 illustrates situations of pneumococcal vaccine prescription by Moroccan rheumatologists. <h3>Conclusion</h3> This survey illustrates a lack of pneumococcal vaccinal prescription by Rheumatologists and suggests the necessity to improve rheumatologists' knowledge concerning pneumococcal vaccination. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.
The imprinting effect of covid-19 vaccines: an expected selection bias in observational studies
Authors: Susana Monge, Roberto Pastor-Barriuso, Miguel A Hernán
Journal: BMJ (2023)

Recent observational studies have found a higher risk of reinfection with the omicron variant of SARS-CoV-2 in people who received a third covid-19 booster dose. This finding has been interpreted as evidence of immune imprinting of covid-19 vaccines. This article proposes an alternative explanation: that the increased risk of reinfection in individuals vaccinated with a booster compared with no booster is the result of selection bias and is expected to arise even in the absence of immune imprinting. To clarify this alternative explanation, this article describes how previous observational analyses were an attempt to estimate the direct effect of vaccine boosters on SARS-CoV-2 reinfections—an effect that cannot be correctly estimated with observational data. Causal diagrams (directed acyclic graphs), data simulations, and analysis of real world data are used to illustrate the mechanism and magnitude of this bias, which is the result of conditioning on a collider.
David Oliver: The “40 new hospitals” pledge was always a mirage
Authors: David Oliver
Journal: BMJ (2023)

In 2020, when he was prime minister, Boris Johnson pledged to build "40 new hospitals by 2030," with a "further eight schemes invited to bid for future funding" as "part of a package worth £3.7bn." 1 This also formed a key part of his 2019 election manifesto. 2 News last week that building works had stalled and that this promise would not be met illustrated serious failings at the heart of government. 3 Which is bad news when the NHS is so politicised and centralised.
A refresh of the top 10 research priorities in cystic fibrosis
Authors: Nicola Jane Rowbotham, Sherie Smith, Zoe C Elliott, Belinda Cupid, Lorna J Allen, Katherine Cowan, Lucy Allen, Alan Robert Smyth
Journal: Thorax (2023)

In 2018 we published the James Lind Alliance (JLA) top 10 priorities for clinical research in cystic fibrosis (CF), chosen jointly by the patient and clinical communities. These priorities have led to new research funding. To establish whether priorities have changed with novel modulator therapies, we undertook an online international update through a series of surveys and a workshop. Patients and clinicians (n=1417) chose the refreshed top 10 from 971 new research questions (suggested by patients and clinicians) and 15 questions from 2018. We are working with the international community to promote research based on these refreshed top 10 priorities.
Pseudonictitating Membrane
Authors: Nisha Ahuja, Pushkal Katara
Journal: Ophthalmology (2023)

A 69-year-old man presented with a membrane over the bulbar conjunctiva in his right eye (OD), encroaching cornea from the temporal side, and freely movable over the conjunctival and corneal surface (A). Extraocular movements were free. The patient had no history of pain, foreign body sensation, lacrimation, chronic illness, prior hospitalization, trauma, adverse drug reaction, or chemical injury. The Schirmer's test showed normal tear film production. The patient had cataracts in both eyes, otherwise, anterior segment and fundus findings were normal. Uncorrected visual acuity was 6/36 OD and 6/18 in the left eye (OS). Intraocular pressure was 16 mmHg OD and 15 mmHg OS, respectively. Image of OD with membrane in (B) primary gaze, (C) down and out position, and (D) up and inwards (Magnified version of Figure A-D is available online at www.aaojournal.org).
Evaluation of RNAi therapeutics VIR-2218 and ALN-HBV for chronic hepatitis B: Results from randomized clinical trials
Authors: Ed Gane, Young-Suk Lim, Jae B. Kim, Vasant Jadhav, Ling Shen, Anna I. Bakardjiev, Stephen A. Huang, Andrea L. Cathcart, Florian A. Lempp, Maja M. Janas, Daniel J. Cloutier, Charalambos Kaittanis, Laura Sepp-Lorenzino, Gregory Hinkle, Jorg Taubel, Patrick Haslett, Stuart Milstein, Yesseinia I. Anglero-Rodriguez, Christy M. Hebner, Phillip S. Pang, Man-Fung Yuen
Journal: Journal of Hepatology (2023)

Background & Aims Current treatment for chronic hepatitis B virus (cHBV) infection requires lifelong treatment. New therapy aimed towards HBV functional cure would represent a clinically meaningful treatment advancement. ALN-HBV and VIR-2218 (modified from ALN-HBV by Enhanced Stabilization Chemistry Plus technology reducing off-target, seed-mediated binding while maintaining on-target antiviral activity) are investigational RNAi therapeutics that target all major HBV transcripts. Methods We report the safety of single doses of VIR-2218 and ALN-HBV in humanized mice, a cross-study comparison of single doses of VIR-2218 and ALN-HBV safety in human heathy volunteers (n=24 and n=49, respectively), and the antiviral activity of two monthly doses of 20, 50, 100, 200 mg of VIR-2218 (total n=24) vs. placebo (n=8) in participants with cHBV infection. Results In humanized mice, alanine aminotransferase (ALT) levels were markedly lower following administration with VIR-2218 compared with ALN-HBV. In healthy volunteers, posttreatment ALT elevations occurred in 28% of participants receiving ALN-HBV compared with none in those receiving VIR-2218. In participants with cHBV infection, VIR-2218 was associated with dose-dependent reductions in hepatitis B surface antigen (HBsAg). The greatest mean reduction of HBsAg at Week 20 in participants receiving 200 mg was 1.65 log IU/mL. The HBsAg reduction was maintained at 0.87 log IU/mL at Week 48. No participants had serum HBsAg loss or hepatitis B surface antibody seroconversion. Conclusions VIR-2218 demonstrated an encouraging hepatic safety profile in preclinical and clinical studies as well as dose-dependent HBsAg reductions in patients with cHBV infection. These data support future studies with VIR-2218 as part of combination regimens with a goal of HBV functional cure. Trial registration ClinicalTrials.gov Identifier: NCT02826018 and NCT03672188
Preliminary results from a phase I/II study of IMM0306, a CD47 and CD20 bispecific monoclonal antibody-trap, in patients with relapsed or refractory CD20-positive B-cell non-Hodgkin's lymphoma.
Authors: Jianliang Yang, Yongping Song, Zhiming Li, Mingzhi Zhang, Keshu Zhou, Zhen Wang, Hongmei Jing, Li Yu, Huizi Ma, Xiwen Zhao, Wei Li, Wei Meng, Wenzhi Tian, Yuankai Shi
Journal: Journal of Clinical Oncology (2023)

7527 Background: IMM0306 is a fusion protein of CD20 monoclonal antibody with the CD47 binding domain of SIRPα on both heavy chains. It has a higher affinity for CD20 than for CD47, thus enabling its preferential and simultaneous binding to CD20 and CD47 on malignant B cells rather than to CD47-postive normal tissues. Here, we report the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy results of the dose escalation stage in a phase I/II study in patients (pts) with relapsed or refractory CD20-positive B-cell non-Hodgkin's lymphoma. Methods: This is a first-in-human, open-label, phase I/II study of IMM0306. The ongoing Phase I part (0.04, 0.1, 0.25, 0.5, 0.8, 1.2, 1.6, 2.0 mg/kg, IV) followed an accelerated titration and standard 3+3 design. IMM0306 was administered once per week after a 2-week single-dose period, until disease progression or intolerable toxicity. Dose-limiting toxicity (DLT) was evaluated in the first 28 days. Safety was evaluated per CTCAE 5.0, tumor assessments performed once every 8 weeks, PK and PD were also assessed. Results: As of the data cut-off date on Dec 15 th , 2022, 42 pts were enrolled. 18 (43%) pts received 3 or more prior lines of therapy, all pts received prior anti-CD20 therapy. No DLTs were observed up to 2.0 mg/kg. The most frequent treatment related adverse events (TRAEs) were lymphocyte decreased (61.9%), white blood cell (WBC) decreased (61.9%), anemia (59.5%), neutrophil (ANC) decreased (40.5%), platelet (PLT) decreased (40.5%), infusion-related reactions (31.0%). Grade ≥ 3 TRAEs occurred in 30 (71.4%) pts, the most frequent grade ≥ 3 TRAEs were lymphocyte decreased (59.5%), WBC decreased (16.7%), ANC decreased (11.9%). Three treatment related SAEs were PLT decreased (grade 4), chest pain (grade 2) and diarrhea (grade 3). In 38 response evaluable pts, 2 follicular lymphoma (FL) pts achieved CR, 1 marginal zone lymphoma (MZL) pt and 2 FL pts achieved PR and 13 pts showed SD. 26 pts were treated at doses ≥ 0.8 mg/kg, among whom 11 were FL pts. Of these 11 FL pts, 4 (36%) responded including 2 CR both at 1.2 mg/kg and 2 PR at 1.2 and 1.6 mg/kg respectively. IMM0306 exhibited approximate dose-proportional increase in PK exposure from 0.5 to 2.0 mg/kg and no obvious accumulation was observed after repeated dosing. B-cell counts depleted rapidly at doses ≥ 0.8 mg/kg. Elevated cytokines levels were observed after first dosing of IMM0306, but multiple dosing did not stimulate further cytokine activation. Conclusions: IMM0306 was well-tolerated and with a robust preliminary anti-tumor activity especially in pts with R/R FL and MZL. The phase I/II study is ongoing. Clinical trial information: CTR20192612 .
Prevention of chemotherapy-induced neutropenia (CIN) with plinabulin (Plin) vs placebo (Plac) in patients (pts) with non-small cell lung cancer (NSCLC) treated with docetaxel (Doc): A pooled analysis from 3 randomized trials.
Authors: Douglas W. Blayney, Jasmine Hurley, Gabrielle Legaspi, Stephen Duprez, Lan Huang, Ramon W. Mohanlal
Journal: Journal of Clinical Oncology (2023)

e21163 Background: CIN can lead to increased patient/healthcare burden, resource utilization, hospitalizations, and poorer quality of life (QoL). G-CSF has a high incidence of bone pain and mild thrombopenia and is given the day after chemo. Plin, a novel non-G-CSF small molecule, protects the bone marrow stem cell, has minimal bone pain, and protects platelet precursors. Plin is given on the same day as chemo and has NSCLC anticancer efficacy (ESMO 2021, Feinstein). The CIN effects of Doc plus Plin vs Doc with Plac were pooled from 3 NSCLC clinical trials. Methods: Data from randomized trials, phase (Ph) 3 trial 103 (NCT02504489), Ph2/3 trial 105 ( NCT03102606 ), and Ph2 trial 101 (NCT00630110) were pooled. Pts were randomized to either Doc (75mg/m 2 ) plus Plin (20mg/m 2 or its pharmacokinetic equivalent) (n = 146) or Doc plus Plac (n = 296). Doc was administered on day 1 of each 21-day cycle x 4 cycles, and Plin or Plac was administered ~30 minutes after Doc. Neutrophil counts were taken at predose and day (D) 8 of each cycle in studies 101 &amp; 103, and on predose, D1, 2, 6, 7, 8, 9, 10, 15, and 21 in study 105. Pts given G-CSF in D1-D3 were excluded. Duration of severe neutropenia (DSN) was calculated by methods previously reported (ASH 2022, Blayney). All Grade (Gr) and Gr4 neutropenia (N) rates, Absolute N count (ANC), febrile N (FN) rate, and ANC on D8 (‘nadir’) were obtained. QoL scores were obtained in studies 103 and 105 by EORTC QLQ-C30. Patient-reported adverse events (AEs) were collected. Results: Pt demographics were comparable. Plin was statistically and clinically significantly superior to Plac for All Gr and Gr4 N frequencies, Day 8 ANC (‘nadir’), and DSN (all had p &lt; 0.0001). Febrile Neutropenia (FN) and infection rates were numerically lower (see table). Fewer pts were treated with antibiotics among pts treated with Plin. Platelet count was unaffected with Plin; grade (gr) 3/4 thrombocytopenia was &lt; 1% with either Plin or Plac. The total frequency of treatment-emergent AEs for Plin vs Plac were 71% vs 80%. QoL scores were similar for Plin and Plac. Conclusions: In 3 independent randomized studies (101, 103, and 105), Plin demonstrated a superior benefit for CIN and showed clinical benefit for infection rate versus Plac. Additionally, Plin has the added benefits of pt convenience (same-day dosing and no additional visits or wearable device), a favorable safety and tolerability profile, anticancer efficacy, and QoL maintenance, which represents a distinct advantage over G-CSF. Clinical trial information: NCT02504489 ; NCT03102606 ; NCT00630110 . [Table: see text]
Total neoadjuvant therapy with mFOLFIRINOX versus preoperative chemoradiation in patients with locally advanced rectal cancer: 7-year results of PRODIGE 23 phase III trial, a UNICANCER GI trial.
Authors: Thierry Conroy, Pierre-Luc Etienne, Emmanuel Rio, Ludovic Evesque, Nathalie Mesgouez-Nebout, Veronique Vendrely, Xavier Artignan, Olivier Bouche, Alice Boileve, Matthieu Delaye, Dany Gargot, Valerie Boige, Nathalie Bonichon-Lamichhane, Christophe Louvet, Christelle De La Fouchardiere, Clotilde Morand, Veronica Pezzella, Eric Rullier, Florence Castan, Christophe Borg
Journal: Journal of Clinical Oncology (2023)

LBA3504 Background: We have reported that neoadjuvant chemotherapy (NACT) with FOLFIRINOX followed by chemoradiotherapy (CRT), surgery, and adjuvant chemotherapy (ACT) significantly improved outcomes in patients (pts) with locally advanced rectal cancer (LARC) compared with pts who received standard CRT, surgery, and ACT. We now report the primary and secondary endpoints with mature follow-up (F/U). Methods: PRODIGE 23 is a phase III randomized clinical trial. Eligible pts had cT3 or cT4, M0 rectal adenocarcinomas &lt;15 cm from the anal verge, age 18-75 years, and WHO PS ≤1. Randomization was stratified by center, T stage, N status, T location, and T extramural spread. Arm A pts received preoperative CRT (50 Gy, 2 Gy/fr; 25 fr + capecitabine), surgery, then ACT for 6 months (mos). Arm B pts received 6 cycles of mFOLFIRINOX, then the same preoperative CRT, surgery and 3 mos of ACT, mFOLFOX6 or capecitabine. From 6/2012 to 6/2017, pts were randomly assigned in Arm A (n=230) and B (n=231) by 35 participating centers. Analysis was performed on intent-to-treat population. For survival outcomes, HR and 95% CI were estimated by a stratified Cox proportional hazard (PH) model. However, we observed non-PH. So we used the restricted mean survival time (RMST) to evaluate the treatment effect (Liang F &amp; al Ann Oncol 2018, Pak K &amp; al JAMA Oncol 2017). Results: With a median F/U of 82.2 mos, death was reported for 55 pts in arm A and 42 in Arm B. All survival endpoints were better for Arm B vs Arm A. The absolute increase in 5-year survival were 7.6% for Disease-Free Survival (DFS), 6.9% for Overall Survival (OS), 9.9% for Metastasis-Free Survival (MFS), and 5.7% for Cancer Specific Survival (CSS) in Arm B compared to Arm A. Survival results at 7 years are presented in the Table. 7-year cumulative incidence of locoregional relapses are 5.3% in arm B vs 8.1% in arm A (p= 0.38). Conclusions: NACT with mFOLFIRINOX followed by CRT, surgery, and ACT significantly improved all outcomes, including OS in pts with LARC vs those who received standard CRT, surgery, and ACT. Clinical trial information: NCT01804790 . [Table: see text]
Oral paclitaxel, carboplatin, and dostarlimab (OPE/Cb/D) without and with trastuzumab in early-stage, high-risk breast cancer: Results from the neoadjuvant I-SPY 2 TRIAL.
Authors: Kay T Yeung, Kevin Kalinsky, Christina Yau, Amy Jo Chien, Judy Caroline Boughey, Erica Michelle Stringer-Reasor, Carla Isadora Falkson, Kathy S. Albain, Ingrid A. Mayer, Meghna S. Trivedi, Rita Nanda, Emily H. Douglas, Coral Oghenerukevwe Omene, Hope S. Rugo, Claudine Isaacs, Beverly Parker, Angela DeMichele, Douglas Yee, Laura Esserman
Journal: Journal of Clinical Oncology (2023)

LBA520 Background: I-SPY 2 is a multicenter trial using response-adaptive randomization within biomarker subtypes including MammaPrint (MP) risk to evaluate novel neoadjuvant agents in high-risk breast cancer. Oral paclitaxel and encequidar (OPE) is an oral combination of paclitaxel (P) with a p-glycoprotein pump inhibitor, encequidar, to enhance gastrointestinal (GI) absorption. Dostarlimab (D) is an anti-PD-1 monoclonal antibody. Methods: Women with tumors ≥ 2.5cm and MP high-risk cancers were screened and treated starting Oct 5, 2020. Treatment included Oral Paclitaxel 205mg/m2 and encequidar 12.9 mg on days 1-3, Carboplatin (Cb) AUC 1.5 on day 1 weekly x 12, and Dostarlimab (D) 500 mg every 3 weeks x 4, followed by doxorubicin/ cyclophosphamide (AC) every 2-3 weeks x 4. The control arm was IV P weekly x 12 followed by AC every 2-3 weeks x 4. For patients with HER2+ disease, weekly Trastuzumab (T) was administered during the first 12 weeks. The arm was eligible for graduation [&gt; 85% chance of success in a 300-person phase 3 neoadjuvant trial with a pathologic complete response (pCR) endpoint] in 10 predefined signatures. Results: 106 patients (44 HR+HER2-, 56 HR-HER2- (TN), 6 HER2+) received OPE/Cb/D ± T. The control arm included 388 historical controls (201 HR+HER2-, 156 TN, 31 HER2+). 22 patients (20 HR+, 2 HR-) in OPE/Cb/D were MP1 (MP high) and 84 patients (29 HR+, 55 HR-) were MP2 (MP ultra-high). OPE/Cb/D graduated in the TN signature and accrual was stopped. Conclusions: OPE/Cb/D graduated in the TN signature with a higher predicted pCR rate compared to control. OPE and D have been, individually, shown to have efficacy in other settings. The lower-than-expected pCR rate and lower irAEs with triplet therapy (taxane, platinum, immune checkpoint inhibitor [ICI]) in TN compared to prior IV chemo + ICI arms on I-SPY 2 suggests a possible interference of OPE with ICI. Changes in gut microbiome is being investigated as an explanation. Clinical trial information: NCT01042379 . [Table: see text]